208043-53-2Relevant academic research and scientific papers
Discovery and early clinical development of 2-{6-[2-(3,5-dichloro-4- pyridyl)acetyl]-2,3-dimethoxyphenoxy}- N -propylacetamide (LEO 29102), a soft-drug inhibitor of phosphodiesterase 4 for topical treatment of atopic dermatitis
Felding, Jakob,S?rensen, Morten D.,Poulsen, Tina D.,Larsen, Jens,Andersson, Christina,Refer, Pia,Engell, Karen,Ladefoged, Lotte G.,Thormann, Thorsten,Vinggaard, Anne Marie,Hegardt, Pontus,S?hoel, Anders,Nielsen, Simon Feldb?k
, p. 5893 - 5903 (2014/08/18)
Development of orally available phosphodiesterase 4 (PDE4) inhibitors as anti-inflammatory drugs has been going on for decades. However, only roflumilast has received FDA approval. One key challenge has been the low therapeutic window observed in the clin
Process development of the PDE4 inhibitor K-34
Yanagisawa, Arata,Taga, Masashi,Atsumi, Toshiyuki,Nishimura, Koichiro,Ando, Kyoji,Taguchi, Tsuyoshi,Tsumuki, Hiroshi,Chujo, Iwao,Mohri, Shin-Ichiro
, p. 376 - 381 (2012/02/01)
A short and practical synthesis of the PDE4 inhibitor K-34 (1) was developed. This synthesis was achieved in four steps and with a 58% overall yield. The unique spiro acetal was created with exceptionally high yield by utilizing the neighbor carboxylic acid assistance. This synthesis also features efficient ketone construction with 4-pyridinylmethyl anion 9 and ester 18, in which overreaction should be prohibited by quick in situ enolate formation. The overall synthesis was carried out under mild conditions and used a simple procedure suitable for large-scale production.
SUBSTITUTED ACETOPHENONES USEFUL AS PDE4 INHIBITORS
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Page/Page column 46-47, (2008/12/06)
The present invention relates to a compound according to formula: (I); wherein X1, X2, X3, X4 and X5 independently of each other represent -CH- or N; or X3, X4 and X5
Derivatives of benzofuran or benzodioxole
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, (2008/06/13)
An oxygen-containing heterocyclic compound represented by following Formula (I): wherein R1and R2independently represent hydrogen, lower alkyl, cyano, —(CH2)n—E1—CO—G1(wherein E1represents a bond, O, or NH; and G1represents hydrogen, substituted or unsubstituted lower alkyl, OR6, or NR7R8; and n represents an integer of 0 to 4), or the like; R1and R2are combined to represent a saturated carbon ring together with a carbon atom adjacent thereto; or R2, and R11or R13described below are combined to form a single bond; R3represents hydrogen, phenyl, or halogen; R4represents hydroxy, lower alkoxy, or the like; A represents —C(R9)(R10)— or O; B represents O, NR11, —C(R12)(R13)—, or —C(R14)(R15)—C(R16)(R17)—; D represents (i) —C(R18)(R19)—X— (wherein X represents —C(R21)(R22)—, S, or NR23), (ii) —C(R19a)═Y— [Y represents —C(R24)—Z— (wherein Z represents CONH, CONHCH2, or a bond), or N], or (iii) a bond; and R5represents aryl, an aromatic heterocyclic group, cycloalkyl, pyridine-N-oxide, cyano, or lower alkoxycarbonyl; or pharmaceutically acceptable salts thereof.
DERIVATIVES OF BENZOFURAN OR BENZODIOXOLE
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, (2008/06/13)
An oxygen-containing heterocyclic compound represented by following Formula (I): wherein R1 and R2 independently represent hydrogen, lower alkyl, cyano, —(CH2)n—E1—CO—G1 (wherein E1 represents a bond, O, or NH; and G1 represents hydrogen, substituted or unsubstituted lower alkyl, OR6, or NR7R8; and n represents an integer of 0 to 4), or the like; R1 and R2 are combined to represent a saturated carbon ring together with a carbon atom adjacent thereto; or R2, and R11 or R13 described below are combined to form a single bond; R3 represents hydrogen, phenyl, or halogen; R4 represents hydroxy, lower alkoxy, or the like; A represents —C(R9)(R10)— or O; B represents O, NR11, —C(R12)(R13)—, or —C(R14)(R15)—C(R16)(R17)—; D represents (i) —C(R18)(R19)—X— (wherein X represents —C(R21)(R22)—, S, or NR23), (ii) —C(R19a)═Y— [Y represents —C(R24)—Z— (wherein Z represents CONH, CONHCH2, or a bond), or N], or (iii) a bond; and R5 represents aryl, an aromatic heterocyclic group, cycloalkyl, pyridine-N-oxide, cyano, or lower alkoxycarbonyl; or pharmaceutically acceptable salts thereof.
OXYGENIC HETEROCYCLIC COMPOUNDS
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, (2008/06/13)
Oxygen-containing heterocyclic compounds represented by following Formula (I): wherein n represents an integer of 1 to 4; R1, R2, R3and R4are the same or different and represent hydrogen, substituted or unsubstituted lower alkyl, or the like; R5represents hydrogen or halogen; R6represents hydroxy or substituted or unsubstituted lower alkoxy; D represents (1) -C(R8)(R9)-X- or (2) a bond; R7represents (1) substituted or unsubstituted lower alkyl, substituted or unsubstituted cycloalkyl, polycycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted aralkyl, a substituted or unsubstituted aromatic heterocyclic group, a substituted or unsubstituted heterocyclic group, or pyridine-N-oxide, (2) -Y-ZR14, (3) -Y-Z-(CH2)m-N(R16a)R16b, or (4) -Y-CON(R17a)R17b, or pharmaceutically acceptable salts thereof.
